Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Molecular Profiling and Real-world Outcomes of BRAF V600E-Mutated Papillary Thyroid Cancer.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chirra Martina, Elliott Andrew, Shaikh Hira, McGrath Julie, El-Gamal Dalia, Karnezis Anthony Nicholas, Abdulla Farah R, Ikpeazu Chukwuemeka, Leddon Jennifer, Sukari Ammar, Zandberg Dan P, Johnson Jennifer Maria, Sun Lova, Wise-Draper Trisha M
Аннотация
PURPOSE: Radioactive iodine-refractory papillary thyroid cancers (PTC) containing BRAF V600E mutations can be treated with BRAF/MEK inhibitors (BRAF/MEKi), but their effectiveness compared with tyrosine kinase inhibitors (TKI) and immunotherapy (IO) remains unclear. Therefore, we compared real-world survival and molecular/transcriptional signatures in patients with BRAF V600E-mutated (BRAF-mut) and BRAF wild-type (WT) PTC.
EXPERIMENTAL DESIGN: Thyroid tumor samples underwent DNA/RNA next-generation sequencing and immunohistochemistry at Caris Life Sciences. Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using quanTIseq. Insurance claims data were used to infer real-world overall survival (OS) and time on treatment.
RESULTS: A total of 1,348 patients with differentiated thyroid cancer were identified; 81.8% were classified as PTC, of which 68.4% harbored a BRAF V600E mutation. TERT promoter mutations were the most common mutation in PTC (72%) and were more prevalent in BRAF-mut versus BRAF-WT. Mutations in NRAS, HRAS, and KRAS, as well as RET, BRAF, and ETV6 gene fusions, were predominantly found in BRAF-WT PTC. BRAF-mut PTC were more often PD-L1+ (33% vs. 18%, P < 0.001) and had significantly higher IFNγ scores. OS was not significantly different between patients with BRAF-mut versus BRAF-WT PTC. Systemic treatment (BRAF/MEKi, TKI, or IO) was not associated with significant differences in OS in BRAF-mut PTC, although there was a trend for longer OS in those treated with TKI compared with BRAF/MEKi or IO.
CONCLUSIONS: BRAF-mut PTC is associated with a proinflammatory TME milieu compared with BRAF-WT PTC. However, in this limited dataset, treatment choice was not associated with differences in OS in BRAF-mut PTC.
EXPERIMENTAL DESIGN: Thyroid tumor samples underwent DNA/RNA next-generation sequencing and immunohistochemistry at Caris Life Sciences. Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using quanTIseq. Insurance claims data were used to infer real-world overall survival (OS) and time on treatment.
RESULTS: A total of 1,348 patients with differentiated thyroid cancer were identified; 81.8% were classified as PTC, of which 68.4% harbored a BRAF V600E mutation. TERT promoter mutations were the most common mutation in PTC (72%) and were more prevalent in BRAF-mut versus BRAF-WT. Mutations in NRAS, HRAS, and KRAS, as well as RET, BRAF, and ETV6 gene fusions, were predominantly found in BRAF-WT PTC. BRAF-mut PTC were more often PD-L1+ (33% vs. 18%, P < 0.001) and had significantly higher IFNγ scores. OS was not significantly different between patients with BRAF-mut versus BRAF-WT PTC. Systemic treatment (BRAF/MEKi, TKI, or IO) was not associated with significant differences in OS in BRAF-mut PTC, although there was a trend for longer OS in those treated with TKI compared with BRAF/MEKi or IO.
CONCLUSIONS: BRAF-mut PTC is associated with a proinflammatory TME milieu compared with BRAF-WT PTC. However, in this limited dataset, treatment choice was not associated with differences in OS in BRAF-mut PTC.